The aim of this study is to enhance our understanding of the interrelated pathways of fatty acid oxidation, fatty acid synthesis and ketone body utilization and their regulation in heart muscle. Initially an ongoing study of the enzymes of Beta-oxidation from pig heart will be completed. Furthermore, the identity of these enzymes with those involved in fatty acid synthesis and ketone body utilization will be investigated. The number of mitochondrial systems of fatty acid synthesis, their intramitochondrial localization and their primer and coenzyme specificities will be determined. In order to study the regulation of the above mentioned pathways, especially that of Beta-oxidation, attempts will be made to determine the rate-limiting steps by measuring the enzymatic activities in homogenates and in whole mitochondria. Subsequently, the effects of possible regulators of these pathways, such as adenine nucleotides, pyridine nucleotides, carnitine and CoA derivatives, on the reaction rates of enzymes which catalyze the rate-limiting steps will be investigated. The physiological significance of results thus obtained will be evaluated by corresponding measurements with whole mitochondria. BIBLIOGRAPHIC REFERENCES: J.C. Fong and H. Schulz, Purification and Properties of Pig Heart Crotonase and the Presence of Short Chain and Long Chain Enoyl Coenzyme A Hydratases in Pig and Guinea Pig Tissues, J. Biol. Chem. 252, 542 (1977). J. F. Binstock, A. Pramanik and H. Schulz, Isolation of a Multi-Enzyme Complex of Fatty Acid Oxidation from Escherichia coli, Proc. Natl. Acad. Sci. USA 74 (1977) in press.